75 articles - From Friday May 27 2022 to Friday Jun 03 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Blood |
The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification (ICC) of mature lymphoid, histiocytic, and dendritic cell tumors. |
meta-analyses and systematic reviews
| Blood Cancer J |
Effectiveness, immunogenicity, and safety of COVID-19 vaccines for individuals with hematological malignancies: a systematic review. Similarly, AEs were rarely reported (0-50.9% =1 AE, 0-7.5% =1 serious AE). In conclusion, HM patients present impaired humoral and cellular immune response to COVID-19 vaccination with disease and treatment specific response patterns. In light of the ongoing pandemic with the easing of mitigation strategies, new approaches to avert severe infection are urgently needed for this vulnerable patient population that responds poorly to current COVID-19 vaccine regimens. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials. |
Treosulfan Compared with Reduced-Intensity Busulfan Improves Allogeneic Hematopoietic Cell Transplantation Outcomes of Older Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients: Final Analysis of a Prospective Randomized Trial. EFS of patients (median age 60 |
| Ann Oncol |
Impact of acetaminophen on the efficacy of immunotherapy in cancer patients. In addition, interleukin-10, a crucial mediator of Treg-induced immune suppression, was significantly upregulated upon treatment with ICB in cancer patients taking APAP. This study provides strong pre-clinical and clinical evidence of the role of APAP as a potential suppressor of antitumor immunity. Hence, APAP should be used with caution in patients treated with ICB. |
Validation of the Decipher Genomic Classifier in Patients receiving Salvage Radiotherapy without Hormone Therapy after Radical Prostatectomy - An Ancillary Study of the SAKK 09/10 Randomized Clinical Trial. This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. This data confirms the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting. |
| Blood |
Anticoagulation in Hospitalized Patients with COVID-19. Three randomized control trials suggesting benefit of therapeutic heparin in hospitalized non-critically ill patients with COVID-19 have led to conditional guideline recommendations for this treatment. By contrast, prophylactic dose heparin is recommended for critically ill patients. Unprecedented collaboration and rapidly funded research has improved care of hospitalized patients with COVID-19. |
DNMT3A mutations define a unique biological and prognostic subgroup associated with cytotoxic T-cells in PTCL-NOS. Furthermore, stable, ectopic expression of the DNMT3A-mutants in primary CD3+ T-cell cultures resulted in the preferential outgrowth of CD8+ T-cells with DNMT3AR882H mutation. Single-cell-RNA-seq analysis of CD3+ T-cells revealed differential CD8+ T-cell subset polarization, mirroring findings in DNMT3A-mutated PTCL-TBX21 and validating the cytotoxic and T-cell memory transcriptional programs associated with the DNMT3AR882H mutation. Our findings indicate that DNMT3A mutations define a cytotoxic subset in PTCL-TBX21 with prognostic significance, thus may further refine pathological heterogeneity in PTCL-NOS and suggest alternative treatment strategies for this subset. |
p57Kip2 regulates embryonic blood stem cells by controlling sympathoadrenal progenitor expansion. To gain further molecular insights, we have generated a single-cell RNA-Seq dataset of al Ngfr+ sympathoadrenal cells around the dorsal aorta to dissect their differentiation pathway. Importantly, this not only defined the relevant p57Kip2-expressing SNS progenitor stage, but also revealed that some neural crest cells, upon arrival at the aorta, are able to take an alternative differentiation pathway, giving rise to a subset of ventrally restricted mesenchymal cells that express important HSC-supportive factors. Neural crest cells thus appear to contribute to the AGM HSC niche via two different mechanisms: SNS-mediated catecholamine secretion and HSC-supportive mesenchymal cell production. |
PLAG1 dampens protein synthesis to promote human hematopoietic stem cell self-renewal. We find PLAG1 capitalizes on multiple regulatory factors to ensure protective diminished protein synthesis including 4EBP1 and translation-targeting miR-127, and does so independently of stress response signaling. Overall, our study identifies PLAG1 as an enforcer of human HSC dormancy and self-renewal through its highly context-specific regulation of protein biosynthesis, and classifies PLAG1 among a rare set of bona fide regulators of mRNA translation in these cells. Our findings showcase the importance of regulated translation control underlying human HSC physiology, its dysregulation under activating demands, and the potential if its targeting for therapeutic benefit. |
Recurrent non-coding somatic and germline WT1 variants converge to disrupt MYB binding in acute promyelocytic leukemia. The high incidence of biallelic inactivation suggested the tumor suppressor activity of WT1 in APL. Mechanistically, non-coding WT1 variants disrupted MYB binding on chromatin and suppressed the enhancer activity and WT1 expression through destroying the chromatin looping formation. Our study highlights the essential role of non-coding variants in the leukemogenesis of APL. |
| Blood Adv |
A Real-World Study of Combined Modality Therapy for Early-Stage Hodgkin Lymphoma: Too Little Treatment Impacts Outcome. Based on our real-world experience, CMT appears beneficial for patients with early-stage cHL, especially those with PET2-positive, and unfavorable disease. Chemotherapy-alone regimens can lead to comparable outcomes for patients with favorable, non-bulky, or PET2-negative disease. We conclude that while results seen in clinical trials are replicated in certain patient subgroups, other subgroups not fitting trial criteria do poorly when radiotherapy is excluded. |
Efficacy and Safety of Avapritinib in Previously Treated Patients with Advanced Systemic Mastocytosis. Avapritinib was effective in al AdvSM subtypes, regardless of number/type of prior therapies or somatic mutations associated with poor prognosis. Treatment-related adverse events (TRAEs) were observed in 94% of patients, most commonly grade 1 or 2; 57% had TRAEs =grade 3; 81% remained on treatment at 6 months. Avapritinib in adults with AdvSM who received prior systemic therapy was generally well tolerated with high response rates regardless of prior systemic therapy. |
High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in CLL patients. The residual signaling capacity downstream of BTK was associated with high expression of sIgM, while it was minimal when sIgM expression was low (p<0.05). These results suggested that high sIgM levels facilitated CLL cell resistance to ibrutinib in patients. The CLL cells, surviving in the periphery with high sIgM expression, include a dangerous fraction, able to migrate to tissue and receive proliferative stimuli, which may require targeting by combined approaches. |
Identification and characterization of RBM12 as a novel regulator of fetal hemoglobin expression. Enhanced crosslinking and immunoprecipitation followed by high throughput sequencing (eCLIP-Seq) revealed strong preferential binding of RBM12 to 5'UTRs of transcripts, narrowing down the mechanism of RBM12 action. Notably, we pinpointed the first of five RRM domains as essential, and, in conjunction with a linker domain, as sufficient for RBM12-mediated HbF regulation. Our characterization of RBM12 as a negative regulator of HbF points to an additional regulatory layer of the fetal-to-adult hemoglobin switch and broadens the pool of potential therapeutic targets for SCD and ß-thalassemia. |
Organ-specific response after low-dose interleukin-2 therapy for steroid refractory chronic Graft-versus-Host Disease. For immunologic correlates, CD4Treg:CD4Tcon ratio at one week was significantly higher in patients with overall and skin response; skin response was significantly associated with lower number of total CD3 T cells, CD4Tcon and CD8 T cells and higher number of B cells. For lung responders, terminal effector memory cell counts were lower within al T cell populations compared to non-responders. Organ-specific mechanisms of injury should be investigated and organ-specific targeted therapies need to be developed. |
p16INK4A dependent senescence in the bone marrow niche drives age-related metabolic changes of hematopoietic progenitors. We found that, in response to LPS induced stress, HPC mitochondrial function is impaired and there is a failure to upregulate the TCA cycle in progenitor populations in aged animals compared to young animals. Furthermore, aged mesenchymal stromal cells (MSC) of the BM niche, but not HPCs, exhibit a senescent phenotype and selective depletion of senescent cells from the BM niche, as well as treatment with the senolytic drug ABT-263, improves mitochondrial function of HPCs when stressed with LPS. In summary, age related HPC metabolic dysfunction occurs indirectly as a 'bystander phenomenon' in the aging BM niche and can be restored by targeting senescent MSCs. |
The Odyssey of Pacritinib in Myelofibrosis. Although the PERSIST-2 study was terminated abruptly due to this clinical hold, it met its splenic response endpoint and demonstrated a trend towards symptom improvement. Subsequent, diligent review of the PERSIST-1 and PERSIST-2 studies did not confirm an excess of severe bleeding or cardiac events on the pacritinib arm. Additionally, the dose finding PAC203 study endorsed the safety and efficacy of 200 mg twice daily leading to the approval of pacritinib for the treatment of MF patients with platelets =50× 109/L. |
| Blood Cancer J |
Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Among patients who received a prior FLT3 TKI in ADMIRAL, a higher CRc rate (52%) and trend toward longer median overall survival was observed in the gilteritinib arm versus the SC arm (CRc |
Structural variants shape the genomic landscape and clinical outcome of multiple myeloma. These data highlight the heterogeneity of transcriptional dysregulation occurring as a consequence of both the canonical and novel structural variants. Further, it shows that the complex rearrangements chromoplexy, chromothripsis and templated insertions are common in MM with each variant having its own distinct frequency and impact on clinical outcome. Chromothripsis is associated with a significant independent negative impact on clinical outcome in newly diagnosed cases consistent with its use alongside other clinical and genetic risk factors to identify prognosis. |
| Haematologica |
APOLD1 loss causes endothelial dysfunction involving cell junctions, cytoskeletal architecture, and Weibel-Palade bodies, while disrupting hemostasis. Compromised vascular integrity resulting from an excess of plasma ANGPT2, and locally impaired availability of VWF may explain the unusual clinical profile of APOLD1:p. R49* patients. In summary, our findings identify APOLD1 as an important regulator of vascular homeostasis and raise the need to consider testing of EC function in patients with IBDs without apparent platelet or coagulation defects. |
High-risk stage IIB Hodgkin lymphoma treated in the H10 and AHL2011 trials: TMTV is a useful risk factor to stratify patients at baseline. Notably, among the 16 patients who relapsed, 13 (81%) had a baseline TMTV baseline = 155 mL. Upfront ABVD plus radiation therapy or upfront escBEACOPP without radiotherapy provide similar patient's outcome in high-risk stage IIB HL. TMTV is useful to stratify these patients at baseline. |
Treatment of chemotherapy-induced thrombocytopenia in patients with non-hematologic malignancies. Thrombopoietic growth factors (recombinant human thrombopoietin, pegylated human megakaryocyte growth and development factor, romiplostim, eltrombopag, avatrombopag and hetrombopag) improve pretreatment and nadir platelet counts, reduce the need for platelet transfusions, and enable chemotherapy dose intensity to be maintained. National Comprehensive Cancer Network guidelines permit their use but their widespread adoption awaits adequate phase III randomized, placebo-controlled studies demonstrating maintenance of relative dose intensity, reduction of platelet transfusions and bleeding, and possibly improved survival. Their potential appropriate use also depends on consensus by the oncology community as to what constitutes an appropriate pretreatment platelet count as well as identification of patient-related and treatment variables that might predict bleeding. |
| Lancet Haematol |
Activity and safety of topical pimecrolimus in patients with early stage mycosis fungoides (PimTo-MF): a single-arm, multicentre, phase 2 trial. Further controlled clinical trials are warranted to confirm these results. Instituto de Salud Carlos III and the European Regional Development Fund. For the Spanish translation of the abstract see Supplementary Materials section. |
| Leukemia |
Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial. Treatment-emergent adverse events (TEAEs) were consistent with 12-month data. After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML. |
Clonal evolution after treatment pressure in multiple myeloma: heterogenous genomic aberrations and transcriptomic convergence. Single sample GSEA (ssGSEA) scores of differentially expressed pathways revealed that these changes were most evident in end-stage disease. Increased expression of several potentially targetable genes was found at late disease stages, including cancer-testis antigens, XPO1 and ABC transporters. Our study demonstrates a transcriptomic convergence of pathways supporting increased proliferation and metabolism during disease progression in MM. |
Elucidating the importance and regulation of key enhancers for human MEIS1 expression. We further show direct binding of FLI1 to the MEIS1 locus in human AML cell lines as well as enrichment of histone acetylation in MEIS1-high healthy and leukemic cells. We also observe a positive correlation between high FLI1 transcript levels and worse overall survival in AML patients. Our study expands the role of ETS factors in AML and our model constitutes a feasible tool for a more detailed understanding of transcriptional regulatory elements and their interactome. |
Histone demethylase KDM4C is a functional dependency in JAK2-mutated neoplasms. These findings led to reduced disease penetrance and improved survival in xenograft models of human JAK2-mutated cells. KDM4C deleted cells showed alterations in target histone residue methylation and target gene expression, resulting in induction of cellular senescence. In summary, these data establish KDM4C as a specific dependency and therapeutic target in JAK2-mutated cells that is essential for oncogenic signaling and prevents induction of senescence. |
Predictive scoring systems for molecular responses in persons with chronic phase chronic myeloid leukemia receiving initial imatinib therapy. Male sex, higher WBC concentration, lower haemoglobin concentration, higher percentage blood blasts and larger spleen size were significantly-associated with lower cumulative incidences of MMR and MR 4 in training dataset. Using Fine-Gray model, we developed the predictive scoring systems for MMR and MR 4 which classified subjects into the low-, intermediate- and high-risk cohorts with significantly-different cumulative incidences of MMR and MR 4 with good predictive discrimination and accuracy in training and validation cohorts with high area under the receiver-operator characteristic curve (AUROC) values. These data may help physicians decide appropriateness of initial imatinib therapy. |
Regulation of proton partitioning in kinase-activating acute myeloid leukemia and its therapeutic implication. Co-inhibition of NHE1 and kinase synergistically acidified pHi in leukemia and inhibited its growth in vivo. Plasma from patients taking amiloride for diuresis reduced pHi of leukemia and enhanced cytotoxic effects of kinase inhibitors and chemotherapy in vitro. NHE1-mediated intracellular alkalization played a key pathogenetic role in transmitting the proliferative signal from mutated-kinase and could be exploited for therapeutic intervention in AML. |
The bone marrow niche regulates redox and energy balance in MLL::AF9 leukemia stem cells. Deletion of Cxcl12 leads to the accumulation of reactive oxygen species and DNA damage in LSCs, impairing their ability to perpetuate leukemia in transplantation experiments, a defect that can be attenuated by antioxidant therapy. Importantly, our data suggest that this phenomenon appears to be conserved in human patients. Hence, we have identified Prx1+ mesenchymal cells as an integral part of the complex niche-AML metabolic intertwining, pointing towards CXCL12/CXCR4 as a target to eradicate parenchymal LSCs in AML. |
| Thromb Haemost |
Association of Combined Lifestyle and Polygenetic Risk with Incidence of Venous Thromboembolism: A Large Population-Based Cohort Study. Moreover, of the participants with high genetic risk and unfavorable lifestyle, 2.90% developed VTE, versus 0.66% of the participants with low genetic risk and favorable lifestyle (HR: 4.09; 95% CI: 3.48-4.79). No significant interaction between genetic risk and lifestyle factors was observed ( for interaction |
Continuous Infusion of Factor VIII and von Willebrand Factor in Surgery: Trials with pdFVIII LFB or pdVWF LFB in Patients with Bleeding Disorders. pdFVIII and pdVWF administered by CI represent an effective and safe alternative to bolus injections in patients with severe HA or VWD undergoing surgery. |
Joint effect of multiple prothrombotic genotypes and mean platelet volume on the risk of incident venous thromboembolism. The combination of high MPV and prothrombotic genotypes had an additive effect on VTE risk, suggesting there is no biological interaction between these risk factors in the pathogenesis of VTE. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| Blood Cancer J |
High-risk disease in newly diagnosed multiple myeloma: beyond the R-ISS and IMWG definitions. The goal of this review paper is to summarize and compare the various established risk stratification systems, go beyond the R-ISS and international myeloma working group risk stratifications to evaluate specific molecular and cytogenetic abnormalities and how they impact prognosis independently. In addition, we explore the wealth of new genomic information from recent whole genome/exome sequencing as well as gene expression data and review known clinical factors affecting outcome such as disease burden and early relapse as well as patient related factors such as race. Finally, we provide an outlook on developing a new high risk model system and how we might make sense of co-occurrences, oncogenic dependencies, and mutually exclusive mutations. |
| CA Cancer J Clin |
Oncologic emergencies and urgencies: A comprehensive review. Emergent and urgent complications associated with targeted therapeutics, including small molecules, naked and drug-conjugated monoclonal antibodies, as well as immune checkpoint inhibitors and chimeric antigen receptor T-cells, are summarized. Finally, strategies for facilitating same-day direct admission to hospice from the ED are discussed. This article not only can serve as a point-of-care reference for the ED physician but also can assist outpatient oncologists as well as inpatient hospitalists in coordinating care around the ED visit. |
| Haematologica |
Treatment of drug-induced immune thrombocytopenias. While DITP is commonly associated with an increased risk of bleeding, HIT and VITT have a high mortality rate due to the high incidence of thromboembolic complications. A structured approach to drug-associated thrombocytopenia/thrombosis can lead to successful treatment and a lower mortality rate. In addition to describing the treatment of DITP, HIT, VITT, and vaccine-associated immune thrombocytopenia, this review also provides the pathophysiological and clinical information necessary for correct patient management. |
Treatment of inherited thrombocytopenias. On the other hand, it has become evident that some of the mutations responsible for platelet deficiency predispose the patient to serious, potentially lifethreatening diseases. Today's vision of IT is, therefore, very different from that of the past and the therapeutic approach must take these changes into account while also making use of the new therapies that have become available in the meantime. This review, the first devoted entirely to IT therapy, discusses how to prevent bleeding in those patients who are exposed to this risk, how to treat it if it occurs, and how to manage the serious illnesses to which patients with IT may be predisposed. |
| Lancet Haematol |
| Leukemia |
Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations. Because of the large inter-individual variations in MTX/6-MP bioavailability and metabolism, dose adjustments are traditionally guided by the degree of myelosuppression, but this does not accurately reflect treatment intensity. DNA-TG is a common downstream metabolite of MTX/6-MP combination chemotherapy, and a higher level of DNA-TG has been associated with a lower relapse hazard, leading to the development of the Thiopurine Enhanced ALL Maintenance (TEAM) strategy-the addition of low-dose (2.5-12.5 |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| Lancet Haematol |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |